There are approximately four thousand different genetic diseases, many highly debilitating and frequently resulting in death at an early age. Because almost all of these diseases involve a defective protein, conventional treatment is difficult. A direct approach to treating such diseases involves providing a competent gene in the proper cells to compensate for the mutation. This requires some form of effective transfection process. Transfection is a process whereby a nucleic acid, primarily DNA, is transferred to a target cell and codes for an expressed protein. Transfection is implemented typically to modify the gene complement of the recipient cell for controlled expression of a particular gene. The means by which “foreign” DNA can be packaged and delivered to a host cell are many and varied. The most efficient of these make use of viruses, but viral vectors have shortcomings, not the least of which is the potential for immune response or disease transmission. It has become apparent that lipid-like compounds (e.g., lipoids) can be used to deliver DNA to cells. The lipoids that are most efficient in delivering DNA to cells are positively charged. Cationic lipoids are naturally attracted to and spontaneously form complexes with polyanionic DNA. Such complexes, or “lipoplexes,” are useful as transfection vehicles both in vitro and in vivo. Lipoplexes offer several advantages in that they provide a high DNA packing density, lower immunogeneicity, and are likely to be able to transport DNA of considerably larger size than the viral vectors. The possibility of targeting lipidic carriers to specific cell types also makes them attractive candidates for gene therapy. However, the delivery of whole genes is not the only form of gene therapy. Previous research has demonstrated that antisense gene therapy may be useful to inhibit expression of genes that cause disease. Additionally, recent research on the RNAi effect has shown that administration of particular RNA oligonucleotides could be an especially effective way of silencing genes that are deleterious. Similarly, it has become newly appreciated that DNA oligonucleotides engineered for high affinity binding to particular gene sequences may be useful in gene therapy given the proper delivery system. These kinds of developments make it clear that gene therapy is likely to evolve in a variety of different ways and that different modes will be effective with different diseases.
To date, the primary approach to improving the transfection properties of cationic lipids has been the synthesis of new kinds of cationic amphipaths or the inclusion of non-cationic helper lipids. While such approaches have met with some success, improved transfection reagents that provide efficient transfection (e.g., efficient nucleic acid uptake, low toxicity) are needed.